Breast cancer Drugs:

Breast cancer is a cancer that starts in
the tissues of the breast.

There are two main types of breast

Ductal carcinoma starts in the tubes
(ducts) that move milk from the breast
to the nipple. Most breast cancers are
of this type.
Lobular carcinoma starts in parts of the
breast, called lobules, that produce

Breast cancer is diagnosed in more
than 230,000 women in the U.S. each
year, making it the most common tumor
type, and kills almost 40,000.
More than 160,000 American women
have metastatic breast cancer, which
has spread to other parts of the body,
according to patient advocacy group
Metastatic Breast Cancer Network. The
disease is currently considered

In December 2011 Roche  impressed
specialists and analysts with the news
that pertuzumab combined with
Herceptin and chemotherapy slowed
tumor development for a median of
slightly more than six months--from 8.5
months to 12.4 months. And Novartis's
Afinitor demonstrated a four-month
delay in disease progression among
metastatic patients.

About 25 percent of breast cancers are
driven by HER2, a protein that tells
malignant cells to grow and spread
throughout the body. Roche’s
Herceptin, the first medicine approved
to directly target HER2 positive
cancers, blocks its receptors on the
outside of the cell. Pertuzumab stops
the protein from joining with HER3 and
squelching an even stronger growth

The pertuzumab study, dubbed
Cleopatra, shows using two drugs to
block HER2 are better than one, said
Harold Burstein, a breast oncologist at
Dana-Farber Cancer Institute in
Boston. The cancer resumed growing
after 18.5 months in women getting all
three drugs, compared with 12.4
months for those who didn’t get
pertuzumab in the study involving 808

“It’s great to see such a dramatic
improvement in progression free
survival with hardly any toxicity, and an
emerging signal of a survival
advantage,” Burstein said in an
interview. “Everyone expects FDA will
approve pertuzumab on this data and it
will become a widely used treatment

Roche said it had recently filed with
European regulators for approval to
market pertuzumab for advanced
breast cancer and expects to file soon
in the U.S.

Afinitor by Novartis which has been
approved  for other cancers, halted
tumor growth in women for 4.2 months
when it was added to a drug called
exemestane that blocks production of
the hormone estrogen, compared with
using the hormone therapy alone.

Novartis has called an early end to its
phase III study of the effectiveness of
Afinitor (everolimus) tablets in
combination with Aromasin
(exemestane) in women with metastatic
breast cancer, after an interim analysis
revealed that the regimen significantly
extended progression-free survival
(PFS) compared with placebo plus

The randomized, double-blind study—
known as BOLERO-2 involved more
than 700 postmenopausal women, at
195 sites worldwide.

All participants had a disease that has
progressed despite initial endocrine
therapy with the nonsteroidal  
aromatase inhibitors letrozole or

Afinitor targets the mTOR protein in
cancer cells, which is an important
regulator of tumor cell division, blood
vessel growth, and cell metabolism.

The company said that Afinitor
"significantly" extended the time without
tumor growth. "Despite clinical
progress in advanced breast cancer,
most women are either initially resistant
or develop resistance to hormonal
therapy over time," Herve Hoppenot,
Novartis oncology president, said in a
statement. "Based on these study
results, this combination has the
potential to extend the time until
chemotherapy is needed for these

Patients received either continuous
therapy with Afinitor 10 mg/day orally
or placebo plus oral Aromasin 25

A different trial showed that adding the
drug Afinitor (everolimus)  to Herceptin  
( trastuzumab)  can improve treatment
response to Herceptin-based therapies
in some women with HER2-positive
metastatic breast cancer.

In the phase I/II trial yielding these
results, the combined use of the two
agents was studied in 47 women with
HER2-overexpressing metastatic
breast cancer that progressed on
Herceptin-based therapy.

“Herceptin works well for many
patients, but about 30% of those with
advanced disease do not respond to
the drug, even combined with
chemotherapy,” explained Phuong
Khanh Morrow, MD—lead coauthor of
the study and an assistant professor in
the department of breast medical
oncology at The University of Texas M.
D. Anderson Cancer Center in
Houston. “Even if metastatic HER2-
positive breast cancer initially responds
to Herceptin, the disease usually
eventually progresses on standard
Herceptin-based therapy.”

Herceptin resistance has been linked
to activation of the mammalian target of
rapamycin (mTOR) cancer pathway.

However, Afinitor overcomes resistance
by inhibiting mTOR.

The study subjects received Afinitor
daily and  Herceptin every 3 weeks.
The combination treatment resulted in
a clinical benefit rate of 34%, providing
partial response in seven patients
(15%) and persistent stable disease
(lasting 6 months or longer) in nine

Afinitor, known generically as
everolimus, is approved for kidney
cancer and for neuro-endocrine
pancreatic cancer, the type that felled
Apple Inc. founder Steve Jobs.

T-DM1 (trastuzumab emtansine)  IS
In March 2012  Roche said its phase 3
trial pitting trastuzumab emtansine
against a combination of Xeloda, which
it sells, and GlaxoSmithKline's Tykerb
passed one of its two clinical
endpoints. Breast cancer patients who
had already failed Roche's Herceptin
and a taxane, such as Bristol-Myers
Squibb's Taxol, Sanofi's  Taxotere, or
Celgene's  Abraxane, "lived
significantly longer without their
disease getting worse" -- called
"progression-free survival" in scientific

Roche is saving the numbers for a
scientific meeting. But assuming Roche
isn't embellishing the data, it seems
likely trastuzumab emtansine will be
approved after the company applies to
regulatory agencies later in 2012.
ImmunoGen will get a royalty on
trastuzumab emtansine once it's on the
market because it contributed the
emtansine part of the molecule, a toxic
payload attached to Roche's Herceptin

T-DM1 has been shining in clinical
trials involving women with breast
cancer for years, but the FDA handed
back Swiss drug giant Roche's
application for approval of the drug in
August 2010. That application was
made with promising Phase II data on
the treatment, but regulators
apparently want to see results from
larger studies underway.

T-DM1 is truly a two-pronged weapon
against breast tumors. It uses linker
technology from Waltham, MA-based
ImmunoGen  to equip Roche's
Herceptin, an antibody that binds to
HER2-expressing breast tumors, with a
cell-killing agent known as DM1. This
enables the antibody to home in on the
cancer target and deliver the cell-killing
agent into tumor cells.

Preliminary data released in October
2010 from a 137-patient Phase II study
showed that 47.8 percent of breast
cancer patients on T-DM1 had a
confirmed objective response on T-
DM1, compared with 41.4 percent who
were taking a combination of Herceptin
and a chemotherapy drug, taxane.

A compound known as an aromatase
inhibitor cut the breast-cancer risk by
65 percent for women prone to the
disease for any reason, such as having
risky genes, a relative who had the
disease or being older than 60, a study
of more than 4,500 women concluded.

Two drugs, tamoxifen and raloxifene,
are already approved to prevent breast
cancer but are rarely used for that
purpose, in part because they can
have serious side effects such as
uterine cancer and blood clots.

The researchers said the new option,
exemestane sold under the brand
name Aromasin, does not have those
side effects and might be more

The drug is sold by Pfizer Inc   which
lost its patent April 1, 2011 and is now
available in a cheaper generic version.

The study, which was sponsored by
Pfizer, broke participants up into two
groups: One got the drug and the
other got a placebo. There were 11
invasive breast cancers reported in the
drug group compared with 32 in the
placebo group. There were also fewer
cases of precursor lesions in the group
that got exemestane.

A class of drugs called PARP inhibitors
is being tested. By inhibiting PARP, the
drugs make tumor cells more sensitive
to chemotherapy because the PARP
protein is involved in removing
chemotherapy-induced platinum
damage from DNA. Without the repair
mechanism, the tumor cell is more
likely to die.

Abbott Labs has a PARP inhibitor
called veliparib, as does Pfizer . And
Teva Pharmaceuticals  has one as well
through its purchase of Cephalon.

Just don't bet the farm on the
compounds; Sanofi's PARP inhibitor,
iniparib, failed a phase 3 trial earlier in
2011. So did olaparib from

We'll have to see how the data plays
out for the other before we know
whether the mechanism of action
doesn't work of whether iniparib just
wasn't a strong enough inhibitor.

A study tested eribulin, developed by
Eisai Co., a drug derived from a sea
sponge. Unlike Herceptin and other
gene-targeted drugs that have been
the focus of cancer research for the
past decade, this one is a
chemotherapy — a drug that kills
cancer cells, in this case by attacking
cell division in a novel way.